Voltage‐Activated Calcium Channels: Targets of Antiepileptic Drug Therapy?

DOI Web Site Web Site 11 Citations 103 References

Search this article

Abstract

<jats:p><jats:bold>Summary: </jats:bold> Voltage‐gated calcium currents play important roles in controlling neuronal excitability. They also contribute to the epileptogenic discharge, including seizure maintenance and propagation. In the past decade, selective calcium channel blockers have been synthesized, aiding in the analysis of calcium charinel subtypes by patch‐clamp recordings. It is still a matter of debate whether whether any of the currently available antiepileptic drugs (AEDs) inhibit these conductances as part of their mechanism of action. We tested oxcarbazepine, lamotrigine, and felbamate and found that they consistently inhibited voltage‐activated calcium currents in cortical and striatal neurons at clinically relevant concentrations. Low micro‐molar concentrations of GP 47779 (the active metabolite of oxcarbazepine) and lamotrigine reduced calcium conductances involved in the regulation of transmitter release. In contrast, felbamate blocked nifedipine‐sensitive conductances at concentrations significantly lower than those required to modify <jats:italic>N</jats:italic>‐methyl‐<jats:sc>d</jats:sc>‐aspartate (NMDA) responses or sodium currents. Aside from contributing to AED efficacy, this mechanism of action may have profound implications for preventing fast‐developing cellular damage related to ischemic and traumatic brain injuries. Moreover, the effects of AEDs on voltage‐gated calcium signals may lead to new therapeutic strategies for the treatment of neurodegenerative disorders.</jats:p>

Journal

  • Epilepsia

    Epilepsia 38 (9), 959-965, 1997-09

    Wiley

Citations (11)*help

See more

References(103)*help

See more

Keywords

Report a problem

Back to top